The objective of this research program is to evaluate polyamine metabolism and/or function as a potential target in cancer chemotherapy. Although these molecules and their biosynthetic enzymes are known to be elevated in, and presumably involved in, cell proliferation, their critical significance in this process has not yet been established. By investigating the mechanism of action of methylglyoxal-bis (guanylhydrazone) (MGBG) an agent used successfully in the treatment of leukemias and solid tumors, both of the aforementioned problems can be approached. The drug effectively inhibits cell proliferation, acts as a potent inhibitor of spermidine biosynthesis and, in addition, has recently been found to affect the ultrastructure and function of mitochondria. Possible interrelationships between each of these drug actions are currently being sought. It now seems probable that MGBG- induced mitochondrial effects are responsible for the antiproliferative action of the drug. Means are being sought by which this new understanding of the action of MGBG may be utilized to enhance the chemotherapeutic usefulness of the drug. In particular, the various relationships of MGBG to the polyamines may be exploited in this regard.